The goal of these studies is to identify the ionic currents that underlie salivary gland ductal function and to elucidate the intracellular factors that regulate these currents. The approach .Is to use the electrophysiological technique of patch clamping in order to complement and extend findings made using radiotracer techniques. The hypotheses to be tested are derived from results obtained in our preliminary studies, and from previous electrophysiological studies of salivary gland acinar cells, and generally test whether the same ionic currents and current regulating mechanisms present in acinar cells are also present in ductal cells. The studies utilize whole-cell current measurements from unstimulated and muscarinically stimulated HSG-PA tissue culture cells, and single channel current measurements on excised membrane patches from these cells. The whole-cell current studies allow analysis and characterization of resting cell membrane conduc- tances as well as effects of various intracellular agents involved in cell signaling such as G-proteins, IP3, Ca ion concentrations, protein kinase C and calmodulin. The single channel current studies will allow a definitive characterization of the potassium (and possibly the Cl) channels present in these cells.